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ORIGINAL RESEARCH Open Access Delayed neuropsychological sequelae after carbon monoxide poisoning: predictive risk factors in the Emergency Department. A retrospective study Giuseppe Pepe 1† , Matteo Castelli 1*† , Peiman Nazerian 1† , Simone Vanni 1† , Massimo Del Panta 1† , Francesco Gambassi 2† , Primo Botti 2† , Andrea Missanelli 2† , Stefano Grifoni 1† Abstract Background: Delayed neuropsychological sequelae (DNS) commonly occur after recovery from acute carbon monoxide (CO) poisoning. The preventive role and the indications for hyperbaric oxygen therapy in the acute setting are still controversial. Early identification of patients at risk in the Emergency Department might permit an improvement in quality of care. We conducted a retrospective study to identify predictive risk factors for DNS development in the Emergency Department. Methods: We retrospectively considered all CO-poisoned patients admitted to the Emergency Department of Careggi University General Hospital (Florence, Italy) from 1992 to 2007. Patients were invited to participate in three follow-up visits at one, six and twelve months from hospital discharge. Clinical and biohumoral data were collected; univariate and multivariate analysis were performed to identify predictive risk factors for DNS. Results: Three hundred forty seven patients were admitted to the Emergency Department for acute CO poisoning from 1992 to 2007; 141/347 patients participated in the follow-up visit at one month from hospital discharge. Thirty four/141 patients were diagnosed with DNS (24.1%). Five/34 patients previously diagnosed as having DNS presented to the follow-up visit at six months, reporting a complete recovery. The following variables (collected before or upon Emergency Department admission) were associated to DNS development at one month from hospital discharge in the univariate analysis: CO exposure duration >6 hours, a Glasgow Coma Scale (GCS) score <9, seizures, systolic blood pressure <90 mmHg, elevated creatine phosphokinase concentration and leukocytosis. There was no significant correlation with age, sex, voluntary exposure, headache, transient loss of cons ciousness, GCS between 14 and 9, arterial lactate and carboxyhemoglobin concentration. The multivariate analysis confirmed as independent prognostic factors GCS <9 (OR 7.15; CI 95%: 1.04-48.8) and leukocytosis (OR 3.31; CI 95%: 1.02- 10.71). Conclusions: Our study identified several potential predictive risk factors for DNS. Treatment algorithms based on an appropriate risk-stratification of patients in the Emergency Department might reduce DNS incidence; however, more studies are needed. Adequate follow-up after hospital discharge, aimed at correct recognition of DNS, is also important. * Correspondence: matte.castelli@inwind.it † Contributed equally 1 Emergency Department, Careggi University General Hospital, Via delle Oblate 1, 50139, Florence, Italy Full list of author information is available at the end of the article Pepe et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2011, 19:16 http://www.sjtrem.com/content/19/1/16 © 2011 Pepe et al; l icensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Co mmons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background Carbon monoxide (CO) is a common c ause of poison- ing, resulting in more than 40.000 cases per year in the United States [1,2]. In Italy, estimated incidence is about 6.000 cases per year (resulting in more than 350 deaths/ year) [3]; in the United Kingdom, about 50 people annually die because of CO-poisoning [ 4]. The real inci- dence is underestimated because the majority of cases go unrecognized or unreported. Presenting symptoms are notoriously aspecific (headache, asthenia, nausea, vomiting, transient loss of consci ousness, altered mental status, coma) and correct diagnosis is a challenge for the emergency physician. Mortality among patients admitted to the hospital is low, and prevention of delayed neuropsychological sequelae (DNS) has become the main goal of treatment. DNS usually develop within some weeks after an initial complete clinical recovery from acute poisoning. The reported incidence varies widely from 3 to 40%, because of the lack of establish ed diagnostic criteria [1-16]. Most frequently described sequelae include a broad spectrum of neurological defi- cits, cognitive imp airments and affective disorders [Table 1] [1-16]. DNS gradually resolve over the the first months but can be permanent in about 25% of cases [1-16]; patients with persistent complaints are usually referred to a specialist for long-term therapy. Patient’s initial presentation does not predict the devel- opment of DNS with certainty, but some variables have been associated to DNS: older age, duration of exposure to CO, longer time to treatment, transient loss of consciousness, coma, abnormal results on early neurop- sychometric testing, severe metabolic acidosis, high arterial lactate level, i ncreased serum levels of neuron- specific enolase (NSE), increased levels of myelin basic protein in the cerebrospinal f luid and early head com- puted tomography (CT) or magnetic resonance (MRI) abnormalities [1,2,5-18]. The preventive role of hyperba- ric oxygen (HBO), administ ered in the acute setting, has been evaluated in several trials [6-13] and one metanaly- sis [14] but results are controversial. In particular there are uncertainties about early identification of patients for whom HBO is most likely to benefit [1,2,15,16]. Treatment algorithms are variablebutitiscurrently recommended to consider HBO administration to patients presenting at le ast one of these signs or symp- toms before or upon hospital admission: coma, seizures, transient loss of consciousness, altered mental status, abnormal neurological signs, myocardial injury and severe metabolic acidosis. It is also considered a thera- peutic option for pregnant women and young children [1,2,15,16]. An elevated carboxyhemoglobin level (>25%; >15% during pregnancy) is still cons idered an appropri- ate indication in some treatment algorithms [2]; how- ever, this value does not reflect poisoning s everity and even high values have not been associated to DNS [1,15,16]. A correct identification of the patients at risk in the Emergency Department (ED) might be useful in order to improve treatment, prevent DNS and allow an appropriate medical follow-up after hospital discharge. We conducted a retrospective study to identify which early clinical and instrumental data, available to the emergency physician, predict the development of DNS. Methods A retrospective medical record review was conducted on all CO-poisoned patients admitted to the ED of Careggi University General Hospital from 1992 to 2007. Carbox- yhemoglobin levels were measured by an arterial blood gas analyzer with a CO-oximete r. A carboxyhemoglobi n level at a dmission greater than 5% in non-smokers and >10% in smokers was considered diagnostic [1,2]; patients with a lower level but with suggestive symp- toms and a confirmed exposure to CO (through the use of ambient CO detect ors by emerge ncy medical services or the presence of relatives or cohabitants with diag- nosed poisoning) were also included. Patients with mixed poisoning (carbon monoxide and drugs, alcohol or cyanide) were excluded. Every patient received high- flow supplemental oxygen in the acute setting. In our hospital CO-poisoned patients are currently treated with HBO according to specific criteria [3] (pregnant women, children <2 years old, presence of GCS <9, seizures, transient loss of consciousness, altered mental status, abnormal neurological signs, evidence of myocardial Table 1 Signs and symptoms of delayed neuropsychological sequelae Neurological sequelae Cognitive and psychological sequelae Parkinson-like syndromes Concentration deficit Gait and motor disturbances Memory loss Bradykinesia Cognitive impairment Intention tremor Dementia Myoclonus Personality changes Dyspraxia Anxiety Dysphasia Extreme emotional lability Ataxia Psychosis Postural instability Depression Vertigo Mania Cortical blindness Insomnia Hearing loss, tinnitus Chorea EEG abnormalities Epilepsy Peripheral neuropathies Recurrent headache Fecal/urinay incontinence References: [1-18]. Pepe et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2011, 19:16 http://www.sjtrem.com/content/19/1/16 Page 2 of 8 injury and severe metabolic acidosis - pH <7.2), but an hyperbaric chamber became available only in 2001. Con- sequently, every patient admitted before 2001, despite poisoning severity, was treated with normobaric oxygen (NBO), defined as supplemental oxygen administration in the highest concentr ations available. The presence of the following variables collected before or upon ED admission was considered: age, sex, duration of CO exposure (>or <6 hours), voluntary or accidental expo- sure, c oma (defined as Glasgow Coma Scale (GCS) <9), transient loss of consciousness, seizures, altered level of consciousness (defined as GCS between 9 and 14), head- ache, postural instability (defined as positive Romberg’s sign), systolic blood pressure <90 mmHg, evidence of myocardial injury (defined as electro cardiographic signs of ischaemia/arrythmias and/or cardiac enzymes eleva- tion), dyspnea, carboxyhemoglobin level, pH, paCO2, paO2 and lactate levels in an arterial blood sample at admission. Haemoglobin (Hb), platelet count (Plt), white blood cell count (WBC), troponin I and creatine phos- phokinase (CPK) concentrat ion in a venous blood sam- ple obtained within 6 hours from admission were also collected; treatment modality (HBO or NBO) was also considered. Every patient was invited to participate in three follow-up visits in a dedicated outpatient clinic at one, six and twelve months from hospital discharge. During the visit a c omplete neurological exam was per- formed and Folstein Mini Mental Status Examination (MMSE) was administered. DNS were defined as the presence of neurological, cognitive or affective disorders [Table 1], developed after hospital discharge. Neurora- diological imaging (head CT/head MRI or SPECT) was proposed to patients suffering from DNS. Statistical analysis We investigated the prognostic value of the analyzed variables for the occurrence of DNS development at one month from hospital discharge. We performed univari- ate analysis in which the variables were compared between patients with DNS and patients with a com- plete clinical recovery. We used Student’ st-testand analysis of variance for continuous variables and Fisher’s test for categorical variables. HBO therapy was consid- ered a categorical variable (yes/not). Univariate analysis was performed using a logistic regression model to esti- mate the odds ratio (OR) of developing DNS, along with 95% confidence interval (CI). Variables significantly related to DNS development were selected, multivariate analysis was performed (stepwise forward regression model) and OR estimated. Then a comparison was per- formed (using Student’s t-test and analysis of variance for continuous variables and Fisher ’s test f or categorical variables) between the group of patients treated with HBO and the group treated with NBO. The potential benefit of HBO (in terms of DNS incidence reduction at one month) was investigated. O nly patients prese nting signs or symptoms currently considered indications for HBO in our hospital were included; patients treated with NBO because of the absence at admission of signs and symptoms considered indications for HBO were excluded. For all tests, two-sided p-values less than .05 were considered statistically significant. In text and tables, variables are expressed as mean ± standard devia- tion (SD). Statistical analysis have been conducted using the SPSS statistical package software, v. 14.0 , SPSS, Chi- cago, Illinois). Results Three hundred fifty seven CO-poisoned patients pre- sented to the ED from 1992 to 2007 (mean age: 41 ± 21 years; males: 160). Ten patients were excluded because of mixed poisoning with drugs (mainly benzodiazepines and antidepressants) or alcohol. More than 65% of patients were transported to the ED by emergency med- ical services. Presenting clinical characteristics were aspecific; the signs and symptoms most commonly reported are listed in Table 2. Evidence of myocardial injury was present in 17.2% of patients; systolic blood pressure <90 mmHg in 1.7%. Severe metabolic acidosis (arterial pH <7.2), dyspnea or cardiac chest pain (defined as the presence of chest pain associated to elec- trocardiographic signs of ischaemia/arrythmias and/or cardiac enzymes elevation) were present in less tha n 6.5% of patients. The cherry pink colour of the skin, tra- ditionally considered distinctive of CO poisoning, was Table 2 Presenting signs and symptoms of acute carbon monoxide poisoning Signs/symptoms in the Emergency Department n = 347 % Headache 203 58.5% Transient loss of consciousness 142 40.9% Sinus tachycardia 90 25.9% Nausea/vomiting 87 25.0% Asthenia 70 20.1% Dizziness 70 20.1% Palpitations 64 18.4% Evidence of myocardial injury 60 17.2% GCS between 14 and 9 53 15.2% Postural instability 37 10.6% GCS <9 29 8.3% Seizures 24 6.9% Dyspnea 22 6.3% Severe metabolic acidosis (pH <7.2) 15 4.3% Cardiac chest pain 6 1.7% Systolic blood pressure <90 mmHg 6 1.7% 347 patients. Pepe et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2011, 19:16 http://www.sjtrem.com/content/19/1/16 Page 3 of 8 present in less than 1% of patients. Sixteen patients (4.6%) we re asymptomatic but w ith diagnostic carboxy- hemoglobin levels. Mean carboxyhemoglobin level at admission was 24.8 ± 10%; this value did not correlate with poisoning clinical severity. Two elderly patients died in the ED (0.57%), both presenting coma, myocar- dial injury and haemodynamic instability. Mean duration of hospitalization was 3.7 ± 2.5 days. Ninety-six/347 (27.6%) patients were treated with HBO, in 3 cases because of pregnancy and in 3 cases because of age <2 years. The remainder patients (251/347, 72.4%) were treated with NBO; patients admitted before 2001 received NBO despite the presence of signs and symp- toms currently considered indications for H BO. One hundred forty one/347 (40.6%) patients were evaluated at 30 days from discharge (mean age: 42 ± 21 years; males: 64); DNS were diag nosed in 34/141 (24.1%). The remainder patients completely recovered and resumed their former occupation after hospital discharge. Only 13/141 patients (9.2%) participated to the follow-up visit at six months from hospital discharg e. Five were pre- viously diagnosed as having DNS and reported a com- plete recovery. None of the patients presented to the visitatoneyear.Mostfrequentsequelaeconsistedof mild cognitive dysfunctions: memory and concentration impairment (25/34), difficulty in calculating (9), writing and reading (5). Mean MMSE score was 24.1 ± 1.7. Fif- teen patients developed recurrent headache. Five patients complained of affective disorders (depression or anxiety) diagnosed by a specialist after hospital dis- charge; three patients suffered from insomnia. Abnormal neurological signs were rare (7/34), mainly related to cerebellar and basal ganglia injury: postural instability, rigidity, bradykinesia, gait disturbances, intention tre- mor, impaired coordination and dysarthria. Dyspraxia, dysphasia and anosmia developed respectively in three, two and one patient. A Parkinson-li ke syndrome wi th severe cognitive i mpairment and urinary incontinence developed in another case (a 66 year s-old male present- ing coma and haemodynamic instability at admissio n). The univariate analysis identified the variables associated to DNS development: CO exposure duration >6 hours (p = 0.03), GCS <9 at admission (p = 0.002), seizures (p = 0.001) and systolic blood pressure <90 mmHg (p = 0.04). A CPK concentration >160 U/L (normal range: 20-160 U/L) and leukocytosis (WBC >10.000/microliter) within 6 hours from admission also resulted associated (p = 0.01 and p = 0.004). There was no correlation with age, sex, suicide attempt, duration of exposure, transient loss of consciousness, GCS between 14 and 9, metabolic acidosis and blood gas analysis abnormalities, in particu- lar carboxyhemoglobin level at admission. HBO admin- istration (55/141 patients, 39%) did not result associated to a significant reduction in the DNS incidence at one month (p = 0.36) [Table 3]. The multivariate analysis confirmed as independent variables predictive of risk GCS <9 (OR 7.15; CI 95%: 1.04-48.8) and leukocytosis within 6 hours from admission (OR 3.31; CI 95%: 1.02- 10.71) [Table 4]. The inclusion of categorical variable “HBO therapy” in the previous multivariate analysis con- firmed the lack of an association between DNS and HBO, confirming at the same time the correlation with leukocytosis and GCS <9. Among the 141 patients who presented to the first follow-up visit, 108 presented at admission signs or sympt oms currently considered indi- cations for HBO in our hospital. Patients admitted before 2001 were treated with NBO, because of the una- vaila bility of an hyperbaric chamber in our hospita l (53/ 108, 49%). The remainder patients (55/108, 50.9%) were treated with HBO. The base-line characteristics of the two groups are reported in Table 5. The DNS incidence at one month was 26.8% (29/108 patients), the differ- ence between the two groups was not statistically sig nif- icant (23.6% in the HBO group vs. 30.1% in the NBO group; p = 0.44). The univariate analysis did not show a signi ficant association between HBO administration and DNS incidence reduction (OR 0.72; IC 95%: 0.30-1.68). Among patients who suffered from DNS, 5(14.7%) did not present at admission signs or symptoms currently considered indications for HBO. Discussion In our study, DNS resulted a relatively frequent compli- cation of CO poisoning (24.1% incidence at 30 days from hospital discharge) although clinically mild in most cases. Mortality among CO poisoned patients admitted to the hospital was low (0.57%). We identified several clinical and instrumental data asso ciated to DNS develop ment. Prolonged CO exposure, seizures and GCS <9 are expres- sion of severe poisoning with high probability of neurolo- gical injury. A systolic blood pressure <90 mmHg, although significantly correlated with DNS development, was present in only four patients, a number too low to draw definitive conclusions. Increased CPK concentra- tion (>160 U/L) indicates both CO-mediated muscle necrosis and rhabdomyolysis in comatose patients lying on the flo or for a long time. L eukocytosis is a condition that has never been associated to DNS, but this result can be interpreted considering the role of activated leu- kocytes in the pathogenesis of neurological injury, mainly attributable to oxidative stress and inflammation, than to hyp oxia [19,20]. However, considering the limited differ- ence in white blood cell count between the two groups of patients (non-DNS and DNS), our finding does not seem to have a clinically relevant impact. Furthermore, whether antiinflammatory therapy could prevent DNS is unknown [1,16]. On the other hand, we did not find an association between DNS and some variables previously Pepe et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2011, 19:16 http://www.sjtrem.com/content/19/1/16 Page 4 of 8 Table 3 Base-line characteristics of patients and association between variables and DNS development Variables (before or upon ED admission) Patient number = 141 mean ± SD Non-DNS group at one month from hospital discharge (patient n = 107) mean ± SD DNS group at one month from hospital discharge (patient n = 34) mean ± SD p value Age (years) 42 ± 21 41.7 ± 21.7 40.4 ± 15.5 >.05 Sex (male) 64 (45.3%) 53 (49.5%) 11 (32.3%) >.05 Duration of exposure >6 hours 54 (38.2%) 36 (33.6%) 18 (52.9%) .03 Suicide attempt 5 (3.5%) 3 (2.8%) 2 (5.8%) >.05 Hb (g/dL) 14 ± 1.6 14.1 ± 1.16 13.7 ± 1.9 >.05 WBC (per microlitre) 9.87 ± 3.7 9.100 ± 2.900 11.900 ± 4.900 .004 Plt (per microlitre) 234.300 ± 58.300 236.000 ± 61.700 228.000 ± 47.000 >.05 Troponin I (ng/mL) (n = 43) 0.72 ± 3.25 0.88 ± 3.88 (n = 30) 0.33 ± 0.66 (n = 13) >.05 CPK (U/L) (n = 127) 255 ± 763 159 ± 221 (n = 97) 572 ± 1506 (n = 30) .01 Lactate (mmol/L) (n = 82) 1.77 ± 1.46 1.77 ± 1.41 (n = 62) 1.76 ± 1.34 (n = 20) >.05 pH 7.41 ± 0.07 7.40 ± 0.07 7.41 ± 0.07 >.05 paCO2 (KPa) 4.78 ± 0.87 4.82 ± 0.89 4.62 ± 0.74 >.05 paO2 (KPa) 15.33 ± 1.09 14.93 ± 7.34 16.53 ± 10.45 >.05 GCS <9 15 (10.6%) 6 (5.6%) 9 (26.4%) .002 Transient loss of consciousness 75 (53.1%) 53 (49.5%) 22 (64.7%) >.05 Seizures 14 (9.9%) 5 (4.6%) 9 (26.4%) .001 Systolic blood pressure <90 mmHg 4 (2.8%) 1 (0.9%) 3 (8.8%) .04 Postural instability 37 (26.2%) 26 (24.2%) 11 (32.3%) >.05 Headache 79 (56%) 60 (56%) 19 (55.8%) >.05 GCS between 14 and 9 29 (20.5%) 26 (24.2%) 3 (8.8%) >.05 Severe metabolic acidosis (pH <7.2) 11 (7.8%) 6 (5.6%) 5 (14.7%) >.05 Dyspnea 6 (4.2%) 4 (3.7%) 2 (5.8%) >.05 Mean carboxyhemoglobin level at admission (%) 26.3 ± 10 26 ± 10.2 26.4 ± 10.5 >.05 Evidence of myocardial injury 33 (23.4%) 23 (21,4%) 10 (29,4%) >.05 HBO therapy 55 (39%) 44 (41.1%) 11 (32.3%) >.05 141/347 (40,6%) patients participated in the follow-up visit at one month from hospital discharge. Table 4 Predictive risk factors for DNS development Variables Univariate analysis Odds ratio (confidence interval: 95%) Multivariate analysis Odds ratio (confidence interval: 95%) Systolic blood pressure <90 mmHg 10.25 (1.40-73.68) 1.34 (0.04-40.85) Seizures 7.34 (2.53-22.28) 1.65 (0.18-14.85) GCS <9 6.06 (2.04-17,95) 7.15 (1.04-48.8) Leukocytosis (WBC >10.000/ microlitre) 3.13 (1.31-7.95) 3.31 (1.02-10.71) Duration of exposure >6 hours 2.13 (0.87-5.24) 1.28 (0.09-2.9) CPK >160 U/L 1.14 (0.49-2.60) 1.02 (0.4-1.64) Odds ratios for the association of variables with DNS development at one month from hospital discharge. Univariate and multivariate analysis. Pepe et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2011, 19:16 http://www.sjtrem.com/content/19/1/16 Page 5 of 8 correlated with neurological damage in other studies [5-18]; some of them are current indications for HBO (for example, carboxyhemoglobin level, transient loss of consciousness and GCS between 9 and 14). Carboxyhe- moglobin level at admission has a fundamental diag- nostic role, but the lack of prognostic value was confirmed in our study. Carboxyhemoglobin level is influenced by several factors, such as pre-hospital oxy- gen administration and time elapsed between exposure cessation and hospital admission. At the moment, the preventive role of HBO has not been clearly demon- strated, and whether t o use HBO and in which patients remains controversial. It would be useful to revise and implement the current indications for HBO, considering the presence or the lack, in the acute set- ting, of reliable predictors of DNS. Furthermore, it would be i nteresting to evaluate the potential benefit of HBO for patients with signs and symptoms, asso- ciated to DNS development, not currently considered indications for this therapy. The lack of a statistically significant association between HBO administration and DNS incidence reduction was also evident in our study, although a trend in this direction was present [Table 4,5]. The fact that 5/34 patients who suffered from DNS did not present, at admission, signs or symptoms currently considered indications for HBO could be an interesting result. However, these results were influenced by several limitations: patients treated withHBOpresented,onaverage,amoreseverepoi- soning, even excluding the 33/141 patients suffering from mild poisoning who were treated only with NBO because of the absence at admission of signs a nd symp- toms considered indications for HBO [Table 5]; hyperbaric protocols adopted by our hyperbaric medicine specialists were not equal for all patients (mainly because of the lack of specific universally accepted guidelines) and even NBO therapy was variable (in terms of duration and oxygen concentration). Additionally, it was not possible to acquire information about prehospital treatment (in terms of sup- plemental oxygen and/or drugs administration). Table 5 Comparison between DNS incidence among patients treated with NBO and patients treated with HBO. Base- line characteristics of patients (n = 108) Variables (before or upon ED admission) Patient number = 108 mean ± SD OTI group (patient n = 55) mean ± SD OTN group (patient n = 53) mean ± SD p value Age (years) 44 ± 20 40.6 ± 20.4 48.2 ± 21.5 >.05 Sex (male) 50 (50.9%) 23 (41.8%) 27 (50.9%) >.05 Duration of exposure > 6 hours 41 (37.9%) 27 (49.9%) 14 (26.4%) .01 Suicide attempt 4 (3.7%) 3 (5.4%) 1 (1.8%) >.05 Hb (g/dL) 14 ± 1.7 13.8 ± 1.6 14 ± 1.8 >.05 WBC (per microlitre) 10.100 ± 3.890 10.300 ± 4.100 9.800 ± 3.500 >.05 Plt (per microlitre) 226.000 ± 50.000 220.100 ± 45.000 233.000 ± 54.300 >.05 Troponin I (ng/mL) (n = 36) 0.85 ± 3.54 0.98 ± 3.88 (n = 30) 0.22 ± 0.44 (n = 6) >.05 CPK (U/L) (n = 93) 298 ± 867 385 ± 1149 (n = 50) 195 ± 265 (n = 43) >.05 Lactate (mmol/L) (n = 65) 1.94 ± 1.6 2.05 ± 1.78 (n = 43) 1.75 ± 1.1 (n = 22) >.05 pH 7.40 ± 0.08 7.41 ± 0.06 7.39 ± 0.1 >.05 paCO2 (KPa) 4.81 ± 0.94 4.73 ± 0.6 4.89 ± 1.21 >.05 paO2 (KPa) 15.8 ± 8.78 16.7 ± 8.0 14.7 ± 9.4 >.05 GCS <9 15 (13.8%) 9 (16.3%) 6 (11.3%) >.05 Transient loss of consciousness 75 (69.4%) 42 (76.3%) 33 (62.2%) >.05 Seizures 14 (12.9%) 12 (21.8%) 2 (3.7%) .008 Systolic blood pressure <90 mmHg 4 (3.7%) 1 (1.8%) 3 (5.6%) >.05 Postural instability 32 (29.6%) 14 (25.4%) 18 (33.9%) >.05 Headache 54 (50%) 31 (63.6%) 23 (43.3%) >.05 GCS between 14 and 9 29 (26.8%) 14 (25.4%) 15 (28.3%) >.05 Severe metabolic acidosis (pH <7.2) 11 (10.1%) 5 (9%) 6 (11.3%) >.05 Dyspnea 5 (4.6%) 2 (3.6%) 3 (5.6%) >.05 Mean carboxyhemoglobin level at admission (%) 27.7 ± 9.6 25.9 ± 9.41 29.5 ± 9.7 >.05 Evidence of myocardial injury 33 (30.5%) 14 (25.4%) 19 (35.8%) >.05 DNS incidence at one month 29 (26.8%) 13 (23.6%) 16 (30.1%) >.05 Only patients presenting at admission signs and symptoms currently considered indications for HBO therapy in our hospital were selected. Pepe et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2011, 19:16 http://www.sjtrem.com/content/19/1/16 Page 6 of 8 Our study presents some other limitations. First of all, patients’ low compliance with follow up (in particul ar at six and twelve months) influenced the reported inci- dence and clinical characteristics of DNS. The reported incidence w as probably overestimated, considering that compliance to follow-up (especially to the visit at one month) was probably higher in patients suffering from DNS. The even lowe r compliance to the next follow-up visits can be explained considering both the group of patients who completely recovered and the group of symptomatic patients who referred to a specialist; both groups interrupted the follow-up program. Additionally, this limitation did not permit us to identify late-onset DNS and to evaluate their duration. Our diagnostic accuracy was influenced by several factors. First of all, we adopted diagnostic criteria different from other stu- dies because of the lack of established ones. Further- more, only a few patients with DNS were evaluated with CT, MRI or single-photon emission computed tomogra- phy during follow-up. Several abnormal radiological findings associated to DNS have been reported in litera- ture, in particular injuries of the cerebral cortex, white matter, hippocampus and globus pallidus [1,2,16,17], but in our study, the majority of patients consulted a specia- listandunderwentneuroradiological imaging privately, interrupting the follow-up. Conclusions Acute CO poisoning is still a challenge in emergency medicin e: correct diagnosis, optimal treatment and DN S prevention are fundamental goals. There are no estab- lished criteria , if any, for determining the risk for DNS. Appropriate informatio n about DNS should be given to every patient at the moment of hospital discharge, to allow prompt recognition of sequelae. In our study, sequelae were common after recovery from acute CO poisoning. We identified several potential predictive risk factors for DNS development. Early risk-stratification of patients in the Emergency Department might permit an improvement in quality of care, in terms of DNS pre- vention. No clear evidences are available whether or not HBO therapy is beneficial in preventing DNS, and the indications for this treatment in the acute setting remain controversial. Further research is needed to better define the optimal management of CO poisoning. Acknowledgements We acknowledge the Clinical Toxicology Unit staff for general support and follow-up activity. Author details 1 Emergency Department, Careggi University General Hospital, Via delle Oblate 1, 50139, Florence, Italy. 2 Clinical Toxicology Unit, Careggi University General Hospital, Via delle Oblate 1, 50139, Florence, Italy. Authors’ contributions GP, MC, MDP, FG and AM designed the study; GP, MC, MDP, FG, PB and AM reviewed the literature; MC, MDP and AM collected the data; FG, PB and AM performed the follow-up activity; GP, PN and SV performed the statistical analysis; GP, MC, PN, SV, MDP, PB, AM and SG wrote the manuscript. All the authors revised and approved the manuscript. Competing interests The authors declare that they have no competing interests. Received: 15 December 2010 Accepted: 17 March 2011 Published: 17 March 2011 References 1. Tomaszewski C: Carbon monoxide. In Goldfrank’s toxicologic emergencies. Eight edition. Edited by: Goldfrank LR, Flomenbaum NE, Lewin NA, Howland MA, Robert S, Nelson LS. New York: Mc Graw-Hill; 2006:1689-1704. 2. Maloney G: Carbon monoxide. In Tintinalli’s Emergency Medicine, a comprehensive study guide. Edited by: Tintinalli JE, Stapczynski JS, Ma OJ, Cline DM, Cydulka RK, Meckler GD. New York: Mc Graw Hill; 2010:1410-13. 3. 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Ku HL, Yang KC, Lee YC, Lee MB, Chou YH: Predictors of carbon monoxide poisoning-induced delayed neuropsychological sequelae. Gen Hosp Psychiatry 2010, 32:310-4. Pepe et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2011, 19:16 http://www.sjtrem.com/content/19/1/16 Page 7 of 8 19. Thom SR, Bhopale VM, Fisher D, Zang J, Gimotty P: Delayed neuropathology after carbon monoxide poisoning is immune-mediated. Proc Natl Acad Sci USA 2004, 101:13660-5. 20. Thom SR, Bhopale VM, Han ST, Clark JM, Hardy KR: Intravascular neutrophil activation due to carbon monoxide poisoning. Am J Respir Crit Care Med 2006, 174:1239-48. doi:10.1186/1757-7241-19-16 Cite this article as: Pepe et al.: Delayed neuropsychological sequelae after carbon monoxide poisoning: predictive risk factors in the Emergency Department. A retrospective study. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2011 19:16. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Pepe et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2011, 19:16 http://www.sjtrem.com/content/19/1/16 Page 8 of 8 . Grifoni 1† Abstract Background: Delayed neuropsychological sequelae (DNS) commonly occur after recovery from acute carbon monoxide (CO) poisoning. The preventive role and the indications for hyperbaric oxygen therapy in the. ORIGINAL RESEARCH Open Access Delayed neuropsychological sequelae after carbon monoxide poisoning: predictive risk factors in the Emergency Department. A retrospective study Giuseppe Pepe 1† ,. poisoning. Brain Inj 1999, 13:229-43. 18. Ku HL, Yang KC, Lee YC, Lee MB, Chou YH: Predictors of carbon monoxide poisoning-induced delayed neuropsychological sequelae. Gen Hosp Psychiatry 2010,